Why does the neuron goes to such remarkable lengths to counteract the consequences of the potentiating effects of alcohol on BK, by both 1) minimizing the potentiation of gating by ethanol, and further, 2) dramatically reducing message level and current density of the channel? BK channels play a central role in the regulation of neuronal excitability, controlling neurotransmitter release and shaping of action potentials in many brain regions. On a cellular level, BK serves as an integrator of regulatory processes, as it is activated by both voltage and intracellular calcium (Salkoff et al., 2006). This channel has a very high conductance, and sustained activation would likely have serious consequences for nervous system function. Because of its large conductance, potentiation by alcohol of even the small population of channels remaining could be undesirable. A related question is how the nervous system retains normal function in the face of such a large reduction of BK. Indeed, BK knockout mice, while able to survive, are seriously impaired (Sausbier et al., 2004). It is possible that the overall, relative shift to the STREX isoform,
